Pyridazine carboxylic acids and esters

ABSTRACT

Heterocyclic acids andesters useful as inhibitors of mammalian blood platelet aggregation characterized by Formula I or II are disclosed. ##STR1## Formula I compounds are those wherein n is 6-9, R is hydrogen, lower alkyl or an alkali metal ion, and HET 1  is the heterocyclic radical 1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl. 
     Formula II compounds are those wherein R 1  is hydrogen, lower alkyl or an alkali metal ion, and the radical --OCH 2  CO 2  R is attached in the 3 or 4 ring position; and HET 2  is the heterocyclic radical 1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl.

BACKGROUND OF THE INVENTION

This invention generally pertains to heterocyclic carbon compoundshaving drug and bio-affecting properties and to their preparation anduse. In particular, the invention is concerned with various heterocyclicderivatives characterized by Formulas I and II, infra., which areinhibitors of blood platelet aggregation.

U.S. patents relating to the heterocyclic carboxylic acid and esterderivatives disclosed herein are as follows:

Pyridazine compounds in Field of Search 514/247 and 544/239.

King, et al. U.S. Pat. No. 2,712,542 discloses 2-(3-pyridazonyl)-acidshaving analgesic, anticonvulsant, antispasmodic and sedative activitiesof formula (1). ##STR2##

Baetz, U.S. Pat. No. 3,622,576 discloses diphenylpyridazones of formula(2) having psychotropic and analgesic properties. ##STR3##

Houlihan, U.S. Pat. No. 4,162,317 discloses succinic acid esters of4,5-dihydro-3-(2H)-pyridizones having muscle relaxant activity offormula (3). ##STR4##

SUMMARY OF THE INVENTION

In its broadest aspect, this invention is concerned with heterocycliccarboxylic acids and esters of Formula I and Formula II ##STR5## whereinHET₁, HET₂, R, R₁, and n are defined below which are inhibitors ofadenosine diphosphate and collagen-induced aggregation of humanplatelet-rich plasma and are particularly useful as inhibitors ofmammalian blood platelet aggregation.

Another embodiment of the invention relates to the alkali metal salts ofcarboxylic acids of Formula I (R is hydrogen) and Formula II (R₁ ishydrogen). A further embodiment concerns pharmaceutical compositionscomprised of a Formula I or II compound combined with at least onepharmaceutically acceptable excipient. Yet another embodiment relates toa method for inhibiting blood platelet aggregation in a mammal whichcomprises administering a therapeutically effective amount of a compoundof Formula I or an alkali metal salt thereof where R is hydrogen or aFormula II compound or an alkali metal salt thereof where R₁ is hydrogento a mammal in need of such treatment.

DETAILED DESCRIPTION OF THE INVENTION

This invention relates to inhibitors of mammalian blood plateletaggregation of Formula I

    HET.sub.1 --(CH.sub.2).sub.n CO.sub.2 R                    (I)

wherein n is 6-9, R is hydrogen, lower alkyl or an alkali metal ion, andHET₁ is the heterocyclic radical ##STR6##1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl.

The compounds of the instant invention are further characterized byFormula II ##STR7## wherein R₁ is hydrogen, lower alkyl or an alkalimetal ion, and the radical --OCH₂ CO₂ R₁ is attached in the 3 or 4 ringposition;

HET₂ is the heterocyclic radical ##STR8##1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl.

It is understood that as used herein limitations of Formula I and II aredefined as follows.

The term "lower alkyl" refers to a branched or unbranched saturatedhydrocarbon chain containing from 1-4 carbon atoms; specifically,methyl, ethyl, n-propyl, isopropyl, n-butyl, secondary butyl, andtertiary butyl.

The term "lower alkanol" denotes an alcohol having 1-4 carbon atomsdefined by "lower alkyl".

The symbol "Ph" represents phenyl.

The term "alkali metal ion" refers to ions derived from the alkalimetals, most preferably sodium and potassium.

According to the present invention the compounds characterized byFormula I are obtained by a process comprising:

(a) hydrolyzing a compound of Formula (I^(a))

    HET.sub.1 --(CH.sub.2).sub.n CO.sub.2 R.sup.a              (I.sup.a)

wherein HET₁ is as defined above, n is 6-9 and R^(a) is lower alkyl, or

(b) esterifying a compound of Formula (I^(b))

    HET.sub.1 --(CH.sub.2).sub.n CO.sub.2 H                    (I.sup.b)

wherein HET₁ is as defined above and n is 6-9 with a lower alkanol, or

(c) alkylating HET₁ --H wherein HET¹ is as defined above with a compoundof Formula (III)

    X--(CH.sub.2).sub.n CO.sub.2 R.sup.a                       (III)

wherein X is halogen, preferably bromine, n is 6 to 9, and R^(a) islower alkyl.

Scheme 1 below illustrates the foregoing process. ##STR9##

Compounds of Formula I are conventionally prepared as shown in Scheme 1by base-mediated alkylation of the parent heterocycle (III) with a loweralkanol ester of an omega-halogenalkanoic acid (IV) to provide esters(I^(a)). Alkylation can be carried out with sodium hydride, potassiumhydride, potassium t-butoxide in suitable solvents such astetrahydrofuran and dimethylformamide with conditions dependent upon theidentity of the heterocycle and the acidity of the proton beingreplaced. Preferred alkylating conditions employ sodium hydride indimethylformamide (DMF) at room temperature or potassium carbonate inDMF at 110° C. In those instances where the alkylation results inmixtures of regioisomers, separation is readily accomplished bychromatography on silica gel. Structural assignments are made fromconsideration of the ¹ H and ¹³ C NMR spectra. The heterocycles (III)employed as starting material are synthesized by methods reported in thechemical literature or by minor modifications thereof readily apparentto a skilled chemist.

Esters (I^(a)) are converted to the corresponding acids (I^(b)) underthe influence of either aqueous alkali or aqueous acid depending uponthe sensitivity of the heterocycle. Conversely, acids (I^(b)) areconventionally converted to the corresponding esters (I^(a)) by heatingthe acid in a lower alkanol in the presence of an inorganic acid such ashydrochloric, sulfuric and the like.

Alkali metal salts of Formula I carboxylic acids (R is an alkali metalion) are conventionally prepared by dissolving the acid in a suitablesolvent such as methanol, adding a molar equivalent of an alkali basesuch as sodium methoxide, and precipitating the salt or removing thesolvent.

According to the present invention, the compounds characterized byFormula II are obtained by a process comprising:

(a) hydrolyzing a compound of Formula II^(a) ##STR10## wherein HET₂ isas defined above and R₁ ^(a) is lower alkyl; or

(b) esterifying a compound of Formula II^(b) ##STR11## wherein HET₂ isas defined above; or (c) alkylating HET₂ --H wherein HET₂ is as definedabove with a compound of Formula (V) ##STR12## wherein R₁ ^(a) is loweralkyl and X is halogen or an aryl sulfonate; or

(d) alkylating a compound of Formula (VI) ##STR13## wherein HET₂ is asdefined above with BrCH₂ CO₂ R₁ ^(a) wherein R₁ ^(a) is lower alkyl.

The following scheme for preparation of representative compounds ofFormula II illustrates the foregoing process. ##STR14##

Scheme 2 depicts several different approaches for synthesis of compoundsincorporating the aryloxyacetic acid moiety. Direct alkylation ofheterocycle (1) with either bromide (2) or tosylate (TS) (3) availablefrom alcohol (5), was accomplished with sodium hydride in DMF at roomtemperature or potassium carbonate in DMF at 110° C. to furnish esters(6). Alternatively, in some cases, reaction of the heterocycle (1) withalcohol (5) obtained from diol (4) in the presence of diethylazodicarboxylate and triphenylphosphine provided esters (6) under themild conditions characteristic of the Mitsunobu reaction, Synthesis,1-28 (1981). Carboxylic acids (7) were obtained by alkaline hydrolysisof esters (6).

Alkali metal salts of Formula II carboxylic acids (R₁ is an alkali metalion) are conventionally prepared by dissolving the acid in a suitablesolvent such as methanol, adding a molar equivalent of an alkali basesuch as sodium methoxide, and precipitating the salt or removing thesolvent.

As stated above, the compounds of Formula I and Formula II havepharmacological properties which make them particularly useful asinhibitors of blood platelet aggregation.

Platelet aggregation is considered part of a complex physiologicalmechanism for formation of a thrombus in the vascular system.Thromboembolic phenomena, i.e., the formation of thrombi, are involvedin hemostasis and a number of disease states in mammals includingthrombophlebitis, phlebothrombosis, cerebral thrombosis, coronarythrombosis and retinal vessel thrombosis. An increase in propensity forplatelet aggregation, sometimes referred to as platelet adhesiveness, isobserved following parturition, surgical operations such as coronaryartery bypass surgery, organ transplant, angioplasty, prosthetic heartvalve implants to name a few and in ischaemic heart disease,artherosclerosis, multiple sclerosis, intracranial tumors,thromboembolism, and hyperlipemia; refer to A. Poplawski, et al., J.Artherosclerosis Research, 8, 721 (1968). Thus, the compounds of theinvention which have antithrombogenic actions (inhibit blood plateletaggregation) are useful in prevention or treatment of conditionsinvolving platelet aggregation and thrombosis such as the above. Theinstant compounds are also considered to have antimetastatic potentialin view of their platelet inhibition properties.

The pharmacological properties of the instant compounds can bedemonstrated by conventional in vitro and in vivo biological tests suchas the following.

IN VITRO INHIBITION OF HUMAN PLATELET AGGREGATION

The aggregometer method of Born, C.V.R., J. Physiol., (London), 1962,162, 67-68, as modified by Mustard, J. F., et al., J. Lab. Clin. Med.1964, 64, 548-599 was used to assess the in vitro activity of thevarious compounds as to the inhibition of adenosine diphosphate (ADP)and collagen-induced platelet aggregation. The human volunteer donor'sarm is cleansed with 70% ethyl alcohol. A sterile 20 ml syringe andneedle are used to withdraw 20 ml of blood. The blood is immediatelyadded to a test tube containing 3.8% sodium citrate to prevent clotting(1 part citrate to 9 parts blood).

Platelet rich plasma (PRP) was separated by centrifugation for 10minutes at 1000 rpm (140 xg) from citrated (3.8%) human blood. Allglassware used for preparation of PRP is silicon treated. ADP in finalconcentration of 0.5 mcg/mL or 0.05 mL of a collagen suspension preparedaccording to the method described by Evans, G., et al., J. Exp. Med.,1968, 128, 877-894 was used to induce aggregation. The various compoundstested were dissolved in dimethylsulfoxide (DMSO) so that 5 mcl added tothe platelet rich plasma would yield the desired test concentration.Vehicle control trials were done and compared with aggregation inducedin platelet rich plasma containing various concentrations of the testcompounds. Dose response curves were obtained and InhibitorConcentration (IC₅₀) values calculated. In this test, the IC₅₀ valuesfor dipyridamole, a clinically useful antithrombogenic agent, are 512mcg/ml vs. ADP and 245 mcg/ml vs collagen. Results for 50% inhibition ofADP-induced aggregation are given in Tables I and II hereinafter forvarious Formula I and II compounds.

                  TABLE 1                                                         ______________________________________                                        Inhibition of Human Platelet Aggregation                                      of Formula I Compounds (IC.sub.50  mcg/ml)                                    HET.sub.1 - (CH.sub.2).sub.n CO.sub.2 R                                                                            vs. ADP                                  Example HET.sub.1       n      R     mcg/ml                                   ______________________________________                                        1       1,6-dihydro-6-oxo-3,4-                                                                        8      CH.sub.3                                                                            21                                               diphenyl-1-pyridazinyl                                                2       1,6-dihydro-6-oxo-3,4-                                                                        8      H     2.9                                              diphenyl-1-pyridazinyl                                                3       1,6-dihydro-6-oxo-3,4-                                                                        7      CH.sub.3                                                                            7.7                                              diphenyl-1-pyridazinyl                                                4       1,6-dihydro-6-oxo-3,4-                                                                        7      H     1.6                                              diphenyl-1-pyridazinyl                                                ______________________________________                                    

                  TABLE 2                                                         ______________________________________                                        Inhibition of Human Platelet Aggregation                                      of Formula II Compounds (IC.sub.50 mcg/ml)                                     ##STR15##                                                                                                     Vs ADP                                       Example   HET.sub.2       R.sub.1                                                                              mcg/ml                                       ______________________________________                                        5         1,6-dihydro-6-oxo-3,4-                                                                        CH.sub.3                                                                             0.75                                                   diphenyl-1-pyridazinyl                                              6         1,6-dihydro-6-oxo-3,4-                                                                        H      1.0                                                    diphenyl-1-pyridazinyl                                              ______________________________________                                    

The acids are particularly potent inhibitors of ADP-induced aggregationof human platelets. While the esters are generally less active than theparent acid, they are useful as pro-drugs in vivo where they arehydrolyzed to the corresponding acid.

The dosage employed in the therapeutic methods of the instant inventionwill vary with the form of administration, the particular compoundchosen, the subject being tested and the effect desired. Suitableeffective doses in animals range from 0.1-50 mg/kg body weight orallyand from 0.05-10 mg/kg body weight parenterally (generally characterizedas subcutaneous, intramuscular, and intravenous injection). It iscontemplated that the effective unit dose in man will range from 1 to100 mg and preferably from 1 to 20 mg administered one to three times aday. In accordance with conventional clinical practice, the effectivedose can be determined by administering a Formula I or II compound at adosage substantially less than the dose of the compound which is thoughtto be effective and then increasing the dosage in small increments untilthe desired effect is achieved.

In carrying out the instant therapeutic methods, the active ingredientof Formula I or II or alkali metal salts of Formula I and II carboxylicacids are preferably administered with a pharmaceutically acceptablecarrier and such compositions constitute part of the instant invention.Suitable dosage forms for oral use are tablets, dispersible powders,granules, capsules, syrups and elixirs. Examples of parenteral forms aresolutions, suspension, dispersions, emulsions, and the like. Thecompositions for oral use may contain one or more conventionaladjuvants, such as sweetening agents, flavoring agents, coloring agentsand preserving agents, in order to provide a composition of suitablepharmaceutical elegance. Tablets may contain the active ingredient inadmixture with conventional pharmaceutical acceptable excipientsincluding inert diluents such as calcium carbonate, sodium carbonate,lactose and talc; granulating and disintegrating agents such as starchand alginic acid; binding agents such as starch, gelatin and acacia andlubricating agents such as magnesium stearate, stearic acid and talc.The tablets may be uncoated or coated by known techniques to delaydisintegration and absorption in the gastrointestinal tract and therebyprovide a sustained action over a longer period. Similarly, suspension,syrups and elixirs may contain the active ingredient in admixture withany of the conventional excipients utilized for the preparation of suchcompositions such as suspending agents (e.g., methylcellulose,tragacanth, and sodium alginate), wetting agents (e.g., lecithin,polyoxyethylene stearate) and preservatives such asethyl-p-hydroxybenzoate. Capsules may contain the active ingredientalone or admixed with an inert solid diluent such as calcium carbonate,calcium phosphate and kaolin. The injectable compositions are formulatedas known in the art and may contain appropriate dispersing or wettingagents and suspending agents identical or similar to those mentionedabove.

The following examples are given by way of illustration and are not tobe construed as limiting the invention in any way inasmuch as manyvariations of the invention are possible within the spirit of theinvention.

DESCRIPTION OF SPECIFIC EMBODIMENTS

In the following examples, all temperatures are given in degreesCentigrade. Melting points were recorded on a Thomas-Hoover capillarmelting point apparatus and are uncorrected. Proton magnetic resonance(¹ H-NMR) spectra were recorded on a Bruker AM 300, Bruker WM 360 orVarian Gemini 300 spectrometer. All spectra were determined in CDCl₃ orDMSO-d₆ unless otherwise indicated and chemical shifts are reported indelta units downfield from the internal standard tetramethylsilane (TMS)and interproton coupling constants are reported in Hertz (Hz). Splittingpatterns are designated as follows: s, singlet; d, doublet; t, triplet;q, quartet; m, multiplet; br, broad peak; and dd, doublet of doublet.

EXAMPLE 1 Methyl 6-oxo-3,4-diphenyl-1(6H)-pyridazinenonanoate ##STR16##

Sodium hydride (840 mg of a 60% dispersion in oil, 20 mmol) was washedtwice with hexanes, covered with DMF (25 mL) and5,6-diphenyl-3(2H)-pyridazinone (4 g, 16 mmol), obtained according to P.Schmidt, et al., Helvetica Chim. Acta., 37, 134-140 (1954), added. Aftergas evolution had ceased, the mixture was stirred at room temperaturefor 30 minutes before adding methyl 9-bromononanoate (4.45 g, 18 mmol).The mixture was heated briefly to 110° C. to give a solution and thenallowed to cool before being stirred at room temperature for 1 hour. Themixture was diluted with water and extracted with diethyl ether (3×).The combined extracts were washed with water, dried over sodium sulfateand concentrated to leave an oil. Chromatography on a column of silicagel afforded methyl 6-oxo-3,4-diphenyl-1(6H)-pyridazine nonanoate (6.44g, 95%) as an oil.

Anal. Calcd. for C₂₆ H₃₀ N₂ O₃ : C, 74.61; H, 7.22; N, 6.69. Found: C,74.89; H, 7.38; N, 7.23%.

¹ H-NMR (CDCl₃) delta: 1.20 to 1.45 (8H, m), 1.56 (2H, quintet, J=7 Hz),1.85 (2H, quintet, J=7 Hz), 2.23 (2H, t, J=7.5 Hz), 3.59 (3H, s), 4.20(2H, t, J=7 Hz), 6.88 (1H, s) and 7.00 to 7.40 (10H, m).

EXAMPLE 2 6-Oxo-3,4-diphenyl-1(6H)-pyridazinenonanoic acid ##STR17##

A mixture of methyl 6-oxo-3,4-diphenyl-1(6H)-pyridazinenonanoate (6 g,14 mmol), 5N NaOH solution (8.6 mL, 43 mmol) and methanol (100 mL) washeated to reflux on a steam bath. After 30 minutes, the mixture wasconcentrated, diluted with water and acidified to pH=1 with 2N HClsolution. The mixture was extracted with CH₂ Cl₂, the combined extractsdried over sodium sulfate and concentrated to leave an oil thatcrystallized on standing. Recrystallization from a mixture of CH₂ Cl₂and hexanes gave 6-oxo-3,4-diphenyl-1(6H)-pyridazinenonanoic acid (3.92g, 67%) mp 100°-103° C.

Anal. Calcd. for C₂₅ H₂₈ N₂ O₃ : C, 74.23; H, 6.98; N, 6.93. Found: C,74.25; H, 7.13; N, 7.11%.

¹ H-NMR (CDCl₃) delta: 1.20 to 1.50 (8H, m), 1.59 (2H, t), 1.87 (2H,quintet, J=6.5 Hz), 2.29 (2H, t, J=7 Hz), 4.24 (2H, t, J=7 Hz), 6.98(1H, s), 7.00 to 7.40 (10H, m) and 9.83 (1H, bs).

EXAMPLE 3 Methyl 6-Oxo-3,4-diphenyl-1(6H)pyridazinyloctanoate ##STR18##

Reaction of 5,6-diphenyl-3(2H)-pyridazinone and methyl 8-bromooctanoateaccording to the procedure of Example 1 provided the title compound asan oil.

Anal. Calcd. for C₂₅ H₂₈ N₂ O₃ : C, 74.23; H, 6.98; N, 6.93. Found: C,74.23; H, 7.27; N, 7.34.

EXAMPLE 4 6-Oxo-3,4-diphenyl-1(6H)-pyridazinyloctanoic Acid ##STR19##

Hydrolysis of methyl 6-oxo-3,4-diphenyl-1(6H)-pyridazinyloctanoateaccording to the procedure of Example 2 provided the title compound,m.p. 108°-111° C.

Anal. Calcd. for C₂₄ H₂₆ N₂ O₃.0.2H₂ O: C, 73.15; H, 6.76; N, 7.11; H₂O, 0.91. Found: C, 73.20; H, 6.69; N 7.13; H₂ O, 1.16.

EXAMPLE 5 Methyl[3-[2-(1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl)ethyl]phenoxy]acetate##STR20##

Diethyl azodicarboxylate (2.73 g, 2.50 mL, 16 mmol) was added to astirred solution of 5,6-diphenyl-3(2H)-pyridazinone (3.00 g, 12 mmol),methyl [3-(2-hydroxyethyl)-phenoxy]acetate (2.80 g, 13 mmol) andtriphenylphosphine (4.12 g, 16 mmol) in dry THF (75 mL) maintained at 0°C. The ice bath was removed and the mixture stirred at room temperaturefor 1.75 hours before removal of the solvent. The residue waschromatographed twice on columns of silica gel using mixtures of diethylether and hexanes (7:3) and then (3:2) as eluent to give methyl[3-[2-(1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl)ethyl]phenoxyacetate](5.12 g, 98%), contaminated with 0.6 equivalents of 1,2-dicarbethoxyhydrazine, as a white foam.

Anal. Calcd. for C₂₇ H₂₄ N₂ O₄.0.3H₂ O.0.6C₆ H₁₂ N₂ O₄ : C, 66.64; H,5.82; N, 8.13; H₂ O, 0.98. Found: C, 66.45; H, 5.60; N, 7.73; H₂ O,0.42%.

¹ H-NMR (CDCl₃) delta: 1.24 (3H, t, J=7 Hz), 3.17 (2H, t, J=8 Hz), 3.76(3H, s), 4.17 (2H, q, J=7 Hz), 4.49 (2H, t, J=8 Hz), 4.59 (1H, s), 6.77(1H, dd, J=8 Hz, J'=2.5 Hz), 6.83 (1H, d, J=2.5 Hz), 6.93 (1H, s), 6.93(1H, m), 7.00 to 7.10 (4H, m) and 7.15 to 7.40 (8H, m).

EXAMPLE 6[3-[2-(1,6-Dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl)ethyl]phenoxy]aceticAcid ##STR21##

A mixture of methyl[3-[2-(1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl)ethyl]phenoxy]acetate(4.60 g, 11 mmol), 5N NaOH solution (3.20 mL, 32 mmol) and methanol (80mL) was heated to reflux on a steam bath. After 25 minutes, the methanolwas evaporated, the residue diluted with water and acidified to pH=1with 2N HCl solution. A white solid was filtered off and dissolved inCH₂ Cl₂. Addition of diethyl ether gave[3-[2-(1,6-dihydro-6-oxo-3,4-diphenyl)-1-pyridazinyl)ethyl]phenoxy]aceticacid hydrate dichloromethane solvate (2.60 g, 58%), mp 165°-167° C.

Anal. Calcd. for C₂₆ H₂₂ N₂ O₄.0.1H₂ O.CH₂ Cl₂ : C, 63.20; H, 4.76; N,5.46; H₂ O, 0.35. Found: C, 63.41; H, 4.69; N, 5.44; H₂ O, 0.14%.

¹ H-NMR (DMSO-d⁶) delta: 3.06 (2H, t, J=7.5 Hz), 4.37 (2H, t, J=7.5 Hz),4.62 (1H, s), 5.74 (2H, s), 6.65 to 6.90 (3H, m), 6.94 (1H, s), 7.00 to7.45 (11H, m) and 12.96 (1H, bs).

What is claimed is:
 1. A compound of Formula I

    HET.sub.1 --(CH.sub.2).sub.n CO.sub.2 R                    (I)

wherein n is 6 to 9; R is hydrogen or lower alkyl or an alkali metalion; and HET₁ is the heterocyclic radical ##STR22## 1.6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl.
 2. A compound of Formula II##STR23## wherein R₁ is hydrogen, lower alkyl or an alkali metal ion,and the radical --OCH₂ CO₂ R₁ is attached in the 3 or 4 ringposition;HET₂ is the heterocyclic radical ##STR24## 1.6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl.
 3. The compound of claim 1which is methyl 6-oxo-3,4-diphenyl-1(6H)-pyridazinenonanoate.
 4. Thecompound of claim 1 which is oxo-3,4-diphenyl-1(6H)-pyridazinenonanoicacid.
 5. The compound of claim 1 which is methyl6-oxo-3,4-diphenyl-1(6H)pyridazinyloctanoate.
 6. The compound of claim 1which is 6-oxo-3,4-diphenyl-1(6H)-pyridazinyloctanoic acid.
 7. Thecompound of claim 2 which is methyl[3-[2-(1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl)ethyl]phenoxy]acetate.8. The compound of claim 2 which is[3-[2-(1,6-dihydro-6-oxo-3,4-diphenyl-1-pyridazinyl)ethyl]phenoxy]aceticacid.
 9. The method for inhibiting blood platelet aggregation in amammal which comprises administering a therapeutically effective amountof a compound of claim
 1. 10. The pharmaceutical composition forinhibiting blood platelet aggregation comprising a therapeuticallyeffective amount of a compound of claim 1 and a pharmaceutical carrier.11. The method for inhibiting blood platelet aggregation in a mammalwhich comprises administering a therapeutically effective amount of acompound of claim
 2. 12. The pharmaceutical composition for inhibitingblood platelet aggregation comprising a therapeutically effective amountof a compound of claim 2 and a pharmaceutical carrier.